Effects of the gut microbiota on host adiposity are modulated by the short-chain fatty-acid binding G protein-coupled receptor, Gpr41.
The distal human intestine harbors trillions of microbes that allow us to extract calories from otherwise indigestible dietary polysaccharides. The products of polysaccharide fermentation include short-chain fatty acids that are ligands for Gpr41, a G protein-coupled receptor expressed by a subset of enteroendocrine cells in the gut epithelium. To examine the contribution of Gpr41 to energy balance, we compared Gpr41-/- and Gpr41+/+ mice that were either conventionally-raised with a complete gut microbiota or were reared germ-free and then cocolonized as young adults with two prominent members of the human distal gut microbial community: the saccharolytic bacterium, Bacteroides thetaiotaomicron and the methanogenic archaeon, Methanobrevibacter smithii. Both conventionally-raised and gnotobiotic Gpr41-/- mice colonized with the model fermentative community are significantly leaner and weigh less than their WT (+/+) littermates, despite similar levels of chow consumption. These differences are not evident when germ-free WT and germ-free Gpr41 knockout animals are compared. Functional genomic, biochemical, and physiologic studies of germ-free and cocolonized Gpr41-/- and +/+ littermates disclosed that Gpr41-deficiency is associated with reduced expression of PYY, an enteroendocrine cell-derived hormone that normally inhibits gut motility, increased intestinal transit rate, and reduced harvest of energy (short-chain fatty acids) from the diet. These results reveal that Gpr41 is a regulator of host energy balance through effects that are dependent upon the gut microbiota.
Samuel
Buck S
BS
Center for Genome Sciences and Department of Medicine, Washington University School of Medicine, St. Louis, MO 63108, USA.
Shaito
Abdullah
A
Motoike
Toshiyuki
T
Rey
Federico E
FE
Backhed
Fredrik
F
Manchester
Jill K
JK
Hammer
Robert E
RE
Williams
S Clay
SC
Crowley
Jan
J
Yanagisawa
Masashi
M
Gordon
Jeffrey I
JI
D050154:Adiposity; D000818:Animals; D001439:Bacteroides; D004734:Energy Metabolism; D041981:Gastrointestinal Tract / Q000382:microbiology*; D005856:Germ-Free Life; D006801:Humans; D041581:Methanobrevibacter; D051379:Mice; D018345:Mice, Knockout; D019894:Peptide YY / Q000032:analysis; D043562:Receptors, G-Protein-Coupled / Q000502:physiology*; D013559:Symbiosis
C506482:Gpcr41 protein, mouse; D043562:Receptors, G-Protein-Coupled; D019894:Peptide YY